摘要： Similar to glycolysis, glutaminolysis acts as a vital energy source in tumor cells, providing building blocks for the metabolic needs of tumor cells. To capture glutaminolysis in tumors, 18F-(2S,4R)4-Fluoroglutamine ([18F]FGln) and 18F-fluoroboronoglutamine ([18F]FBQ) have been successfully developed for Positron Emission Tomography (PET) imaging, but these two molecules are lack of stability, resulting in undesired yet significant bone uptake. In this study, we found that [18F]FBQ-C2 is a stable Gln PET tracer by adding two more methylene groups to the side chain of [18F]FBQ. [18F]FBQ-C2 was synthesized with a good radiochemical yield (RCY) of 35% and over 98% radiochemical purity. [18F]FBQ-C2 showed extreme stability in vitro, and no defluorination was observed after 2 hours in phosphate buffered saline at 37 °C. The competitive inhibition assay results indicated that [18F]FBQ-C2 enters cells via system ASC and N, similar to natural glutamine, and can be transported by tumor-overexpressed ASCT2. PET imaging and biodistribution results indicated that [18F]FBQ-C2 is stable in vivo with low bone uptake (0.81±0.20%ID/g) and can be cleared rapidly from most tissues. Dynamic scan and pharmacokinetic studies using BGC823-xenograft-bearing mice revealed that [18F]FBQ-C2 accumulates specifically in tumors, with a longer half-life (101.18±6.50 min) in tumor tissues than in other tissues (52.70±12.44 min in muscle). Biodistribution exhibits a high tumor-to-normal tissue ratio (4.8±1.7 for muscle, 2.5±1.0 for the stomach, 2.2±0.9 for the liver and 17.8±8.4 for the brain). In conclusion, [18F]FBQ-C2 can be used to perform high-contrast Gln imaging of tumors and can serve as a PET tracer for clinical research.